EP2571540B1 - Matrice synthétique absorbable renforcée pour applications hémostatiques - Google Patents

Matrice synthétique absorbable renforcée pour applications hémostatiques Download PDF

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Publication number
EP2571540B1
EP2571540B1 EP11784012.4A EP11784012A EP2571540B1 EP 2571540 B1 EP2571540 B1 EP 2571540B1 EP 11784012 A EP11784012 A EP 11784012A EP 2571540 B1 EP2571540 B1 EP 2571540B1
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Prior art keywords
fabric
hemostatic
synthetic
absorbable
synthetic hemostatic
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German (de)
English (en)
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EP2571540A4 (fr
EP2571540A1 (fr
Inventor
Olajompo Moloye-Olabisi
Dhanuraj S. Shetty
Robert W. Van Holten
Degang Zhong
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Ethicon Inc
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Ethicon Inc
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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/36—Blood coagulation or fibrinolysis factors
    • A61K38/363—Fibrinogen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
    • A61K38/482—Serine endopeptidases (3.4.21)
    • A61K38/4833—Thrombin (3.4.21.5)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • A61L15/26—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42—Use of materials characterised by their function or physical properties
    • A61L15/44—Medicaments
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/252—Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/252—Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
    • A61L2300/254—Enzymes, proenzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/418—Agents promoting blood coagulation, blood-clotting agents, embolising agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/04—Materials for stopping bleeding

Definitions

  • the present invention relates to a bioabsorbable hemostat device that is useful as a construct for use in medical devices.
  • hemostatic materials including oxidized cellulosic based material has been used as a dressing in a variety of surgical procedures, including neurosurgery, abdominal surgery, cardiovascular surgery, thoracic surgery, head and neck surgery, pelvic surgery and skin and subcutaneous tissue procedure.
  • multilayered fabrics are used as all purpose pads, wound dressings, surgical meshes, including hernia repair meshes, adhesion prevention meshes and tissue reinforcement meshes, defect closure devices, and hemostats.
  • U.S. Patent No. 5,593,441 to Lichtenstein et al describes a composite prosthesis preferably having a sheet of polypropylene mesh that allows tissue in-growth, such as Marlex® mesh.
  • This reference discloses that other surgical materials that are suitable for tissue reinforcement and defect closure may be utilized, including absorbable meshes such as a polyglactin 910 (Vicryl®) mesh.
  • the composite prosthesis of Lichtenstein et al also has an adhesion barrier, preferably a sheet of silicone elastomer.
  • U.S. Patent No. 5,686,090 to Schilder et al describes the use of a fleece in combination with a nonabsorbable or absorbable film to prevent mis-growths to adjacent tissue and to reduce adhesions.
  • Schilder et al generally discloses that polypropylene, polyester, polyglactin, polydioxanone or poliglecaprone 25 may be used as the fleece material or the film material.
  • Published U.S. Patent Application 2006/00084930, to Dhanaraj et al describes a reinforced absorbable multilayered fabric that can be used in medical devices specifically for tissue engineering applications. The matrix comprises first preparing a repair site for implantation, and then disposing the reinforced absorbable multilayered fabric at site.
  • the first absorbable nonwoven fabric comprises fibers comprising aliphatic polyester polymers, copolymers or blends thereof; while the second absorbable woven or knitted fabric comprises oxidized regenerated cellulose fibers.
  • the cells are seeded onto the 9010 PLGA component of the matrix before it migrates through the nonwoven matrix and comes in contact with the ORC component.
  • the ORC component typically breaks down in about two weeks and the degradation components create an acidic environment that may not be conducive to cell proliferation or viability.
  • the present invention addresses that by having a totally absorbable synthetic matrix that does not create such environment that is not conducive for cell viability
  • U.S. Patent No. 4,626,253 to Broadnax et al describes a device that relates to a surgical hemostat (SURGICEL) for control of bleeding, and more particularly, to a knitted fabric of oxidized cellulose having superior handling and hemostatic properties.
  • U.S. Patent No. 7,666,803 to Shetty et al. describes the method of making or reinforced absorbable multilayered fabric that can be used as a hemostat. The matrix comprises first preparing a repair site for implantation, and then disposing the reinforced absorbable multilayered fabric at site.
  • the first absorbable nonwoven fabric comprises fibers comprising aliphatic polyester polymers, copolymers or blends thereof; while the second absorbable woven or knitted fabric comprises oxidized regenerated cellulose fibers.
  • the method also describes the appropriate densities and thickness that can be used to make the matrix in that particular invention. However in certain applications where both the hemostasis function and an increased mechanical property is required over a longer period of time, the matrix mentioned will not satisfy both the requirements primarily due to its weaker mechanical properties.
  • WO2006/044881 is directed to a multilayered fabric comprising a first absorbable nonwoven fabric and a second absorbable woven or knitted fabric, and its method of manufacture.
  • WO2008/051758 is directed to a method of making a dressing having at least one protein, comprising the steps of applying at least one protein to a dressing via conventional means; and further subjecting the dressing having the protein thereon to pressure ranging from about 2,500 to about 39,500 psi for about 2 to about 6 seconds.
  • the present invention is directed to a synthetic hemostatic fabric comprising at least one hemostatic agent in a single, nonwoven layer of a first absorbable fabric that comprises polyglycolide/polylactide copolymer and a second absorbable fabric that comprises polydioxanone, wherein both fabrics are in staple form and said synthetic hemostatic fabric is free of any cellulosic or oxidized polysaccharide material according to claim 1.
  • the absorbable nonwoven fabric is comprised of fibers comprising aliphatic polyester polymers, copolymers, or blends thereof.
  • the aliphatic polyesters are typically synthesized in a ring opening polymerization of monomers including, but not limited to, lactic acid, lactide (including L-, D-, meso and D, L mixtures), glycolic acid, glycolide, epsilon-caprolactone, p-dioxanone (1,4-dioxan-2-one), and trimethylene carbonate (1,3-dioxan-2-one).
  • monomers including, but not limited to, lactic acid, lactide (including L-, D-, meso and D, L mixtures), glycolic acid, glycolide, epsilon-caprolactone, p-dioxanone (1,4-dioxan-2-one), and trimethylene carbonate (1,3-dioxan-2-one).
  • the present invention is directed to a hemostatic fabric comprising at least one hemostatic agent in a single non-woven layer of a first absorbable fabric that comprises polyglycolide/polylactide copolymer and a second absorbable fabric that comprises polydioxanone, wherein both fabrics are in staple form.
  • the first absorbable fabric can consist essentially of a copolymer of glycolide/lactide at a 90/10 mol/mol composition.
  • the first absorbable fabric can be in the form of a staple having a length from about 1.9 to 6.4 cm (0.75 to 2.5 inches).
  • the second absorbable fabric can be in the form of a staple having a length from 1.9 to 6.4 cm (0.75 to 2.5 inches).
  • One or both of these staples can be crimped, chemically or mechanically.
  • the weight ratio of the first fabric staples to the second fabric staples can be about 70:30.
  • the mixture of staple materials can be compacted to a thickness of about 1.5 mm and a density of about 100 mg/cc.
  • the hemostatic device is substantially free of any oxidized polysaccharide material.
  • the hemostatic agent comprises thrombin.
  • the hemostatic agent on the hemostatic device comprises thrombin and fibrinogen.
  • the present invention is also directed to a method for using the hemostatic fabric described above as a medical device.
  • the medical device described above preferably provides hemostasis when applied to a tissue or wound requiring hemostasis. More particularly, the device can control and abate mild to moderate bleeding within an effective time period of from about 1 to about 10 minutes.
  • the present invention is also directed to a method for manufacturing a hemostatic fabric described above comprising the steps of suspending the thrombin and fibrinogen in a perfluorinated hydrocarbon to form a suspension and applying the suspension to the absorbable nonwoven fabric.
  • the thrombin activity on the hemostatic fabric can range from about 20 to 500 IU/cm2, and the fibrinogen on the dressing can range from about 2 to 15 mg/cm2.
  • the method can further include the step of sterilizing the hemostatic fabric, such as by radiation.
  • the reinforced absorbable fabric is a non-woven material that comprises at least two synthetic polymer fibers and one or more hemostatic agents.
  • the fabric does not include material amounts of cellulosic or oxidized polysaccharides as a separate layer or combined as part of the non-woven layer.
  • cellulosic or oxidized polysaccharides that have previously been used in hemostatic devices include oxidized cellulose and the neutralized derivatives thereof.
  • the cellulose may be carboxylic-oxidized or aldehyde-oxidized cellulose. Regenerated cellulose and a detailed description of how to make oxidized regenerated cellulose is set forth in U.S. Patent No. 3,364,200 , U.S. Patent No. 5,180,398 , and U.S.
  • Patent No. 4,626,253 While such cellulosic derived materials have been shown to enhance hemostasis, the present invention enjoys certain advantages, particularly when used in combination with particulate-form or lyophilized hemostatic agents, such as thrombin and fibrinogen.
  • the first absorbable nonwoven fabric is comprised of fibers comprising polyglycolide/ polylactide copolymer.
  • the first polymeric fiber material consists essentially of a blend of copolymer of glycolide and lactide, such as a copolymer poly (glycolide-co-lactide) (PGLA, 90/10 mol/mol) and polydioxanone (PDO).
  • PGLA copolymer poly (glycolide-co-lactide)
  • PDO polydioxanone
  • the two materials are processed into a single layer of nonwoven fiber material and are preferably combined at a weight ratio of about 80:20 to about 60:40, more preferably about 70:30 of PGLA and PDO.
  • the PLGA to PDO weight ratio in the non-woven blend can be from 10:90 to 90:10, most preferably in the range of 70:30.
  • poly (glycolide-co-lactide) (PGLA, 90/10 mol/mol) is melt-spun into a polymeric fiber.
  • a multi-filament yarn of PGLA is consolidated, crimped and cut into staple having a length of 0.25 to 7.6 cm (0.1 to 3.0 inches), preferably between 1.9 to 6.4 cm (0.75 to 2.5 inches).
  • PDO is melt-spun into polymeric fiber.
  • a multi-filament yarn of PDO is consolidated, crimped and cut into staple having a length of 0.25 to 7.6 cm (0.1 to 3.0 inches), preferably between 1.9 to 6.4 cm (0.75 to 2.5 inches).
  • the mixture of these staple materials consisting essentially of PGLA/PDO with a weight ratio of 70/30 was carded to create a nonwoven batt and then compacted to a thickness of about 0.25 to 2.5 mm, preferably 1.25 to 1.75 mm and a density of 50 to 200 mg/cc, preferably 75 to 125 mg/cc.
  • One method of making the fabric described herein is by the following process.
  • Absorbable polymer fibers having a size of denier per fiber of about 1 to 4, can be consolidated to about 80 to 120 denier multifilament yarn and then to about 800 to 1200 denier yarn, thermally crimped and then cut to staple having a length between about 1.9 to 6.4 cm (0.75 and 2.5 inch).
  • the staple can be fed into a multi-roller dry lay carding machine one or more times and carded into a uniform nonwoven batt, while humidity is controlled between about 20-60% at a room temperature of 15 to 24°C.
  • the uniform nonwoven batt can be made using a single cylinder roller-top card, having a main cylinder covered by alternate rollers and stripper rolls, where the batt is doffed from the surface of the cylinder by a doffer roller and deposited on a collector roll.
  • the reinforced absorbable fabric can then be scoured by washing in an appropriate solvent and dried under mild conditions for 10-30 minutes.
  • the fabric is scoured using solvents suitable to dissolve any spin finish.
  • Solvents include, but are not limited to, isopropyl alcohol, hexane, ethyl acetate, and methylene chloride.
  • the fabric is then dried under conditions to provide sufficient drying while minimizing shrinkage.
  • the hemostat described herein provides and maintains effective hemostasis when applied to a wound requiring hemostasis.
  • Effective hemostasis is the ability to control and/or abate mild to moderate bleeding within an effective time, as recognized by those skilled in the art of hemostasis. Further indications of effective hemostasis may be provided by governmental regulatory standards and the like. Examples of mild to moderate bleeding include, without limitation, bleeding due to spleen resection, liver resection, blunt liver trauma, and blunt spleen trauma.
  • the non-woven substrate described above can include one or more hemostatic agents.
  • Hemostatic agents for purposes of this application, are agents that have a hemostatic effect, more preferably, slow, impede and eventually stop bleeding at the site of the injury.
  • One method for producing a hemostatic effect at the site of an injury is to introduce one or more agents found in the blood clotting cascade process that may react with one another or other agents naturally present in the body.
  • Thrombin has been used for producing a hemostatic effect, while in another embodiment, thrombin and fibrinogen are used together to produce the desired hemostatic effect. Additional components, such as calcium, can also be provided to further enhance the hemostatic effect.
  • the bioabsorbable nonwoven fabric retains solid thrombin and/or solid fibrinogen in powdery, particulate form without separation and with minimal loss of the powder from its surface due in part to the means for the addition of the hemostatic agent(s) and the non-woven nature of the substrate.
  • one or more biologics containing solutions are separately lyophilized. The lyophilized materials are then ground into powders using a superfine mill, ball mill or a cooled blade mill. The powders are weighed and suspended together in a carrier fluid in which the proteins are not soluble.
  • a preferred carrier fluid is a perfluorinated hydrocarbon, including but not limited to HFE-7000, HFE-7100, HFE-7300 and PF-5060 (commercially available from 3M of Minnesota). Any other carrier fluid in which the proteins do not dissolve may be used, such as alcohols, ethers or other organic fluids.
  • the suspension is thoroughly mixed and applied to the absorbable nonwoven fabric via conventional means such as wet, dry or electrostatic spraying, dip coating, painting, or sprinkling, while maintaining a room temperature of about 15 to 24°C and relative humidity of about 10 to 60%, preferably no more than 30%.
  • the single layer dressing is then dried at ambient room temperature and packaged in a suitable moisture barrier container.
  • the dressing having the thrombin and/or fibrinogen contains no more than 25% moisture, preferably no more than 15% moisture, and most preferably no more than 5% moisture.
  • the thrombin and/or fibrinogen may be animal derived, human, or may be recombinant.
  • the thrombin activity on the dressing may be in the range of about 20 to 500 IU/cm 2 , preferably about 20 to 200 IU/cm 2 , and most preferably about 50 to 200 IU/cm 2 .
  • the fibrinogen activity on the dressing may be in the range of about 2 to 15 mg/cm 2 , preferably about 3 to 12 mg/cm 2 , and most preferably about 5 to 10 mg/cm 2 .
  • the amount of thrombin and/or fibrinogen powder is preferably applied to the nonwoven fabric in a sufficient amount to cover its surface such that no area is visibly devoid of coverage. The powder may sit mostly on top of the nonwoven fabric or, more preferably penetrates into the nonwoven fabric.
  • the dressing described herein may be used as an adjunct to primary wound closure devices, such as arterial closure devices, staples, and sutures, to seal potential leaks of gasses, liquids, or solids as well as to provide hemostasis.
  • primary wound closure devices such as arterial closure devices, staples, and sutures
  • the dressing may be utilized to seal air from tissue or fluids from organs and tissues, including but not limited to, bile, lymph, cerebrospinal fluids, gastrointestinal fluids, interstitial fluids and urine.
  • the hemostat described herein has additional medical applications and can be used for a variety of clinical functions, including but not limited to matrix/substrate, i.e., fibrinogen/thrombin coating, tissue reinforcement, and buttressing, i.e., for gastrointestinal or vascular anastomoses, approximation, i.e., to connect anastomoses that are difficult to perform (i.e. under tension), and tension releasing.
  • the hemostat matrix can additionally promote and possibly enhance the natural tissue healing process in all the above events.
  • This dressing can be used internally in many types of surgery, including, but not limited to, cardiovascular, peripheral-vascular, cardio-thoracic, gynecological, neuro- and general surgery.
  • the hemostat can also be used to attach medical devices (e.g. meshes, clips and films) to tissues, tissue to tissue, or medical device to medical device.
  • Poly (glycolide-co-lactide) (PGLA, 90/10 mol/mol) is melt-spun into polymeric fiber.
  • a multi-filament yarn is consolidated, crimped and cut into PGLA staple material having a length of 5.1 cm (2.0 inches).
  • Polydioxanone (PDO) is melt-spun into polymeric fiber.
  • a mono-filament yarn is consolidated, crimped and cut into PDO staple material having a length of 5.1 cm (2.0 inches).
  • the mixture of staple materials of PGLA/PDO are combined at a weight ratio of 70/30 and are carded to create a nonwoven batt and then compacted to a thickness of about 1.5 mm and a density of about 100 mg/cc.
  • a mild to moderate bleeding model was created by making an incision of 15 mm long and 3 mm deep on a swine spleen.
  • One PGLA/PDO matrix as described in Example 1 is applied to the surgical site and tamponade is applied for two minutes. Hemostasis is checked for 30 seconds after the two-minute tamponade. If free flow bleeding is not observed within 30 seconds, the time to hemostasis was noted. If free flow bleeding is observed, a 30-second tamponade is reapplied until hemostasis is achieved or until the testing period reaches ten minutes, which is defined as a failure in hemostasis. All three test samples achieved hemostasis at 3.14 ⁇ 1.26 minutes (Table 1). Table 1. Hemostasis of PGLA/PDO matrix in spleen model Sample # 1 2 3 Mean SD Hemostasis (min) 2.00 2.92 4.50 3.14 1.26
  • the mechanical property of the reinforced fabric is characterized in an in vitro test.
  • the PGLA/PDO matrix material described in Example 1 is cut into strips (approximately 0.95 cm (3/8 inch) wide by 5.1 cm (2 inches) long).
  • the tensile strength of the fabric is then evaluated at dry and wet conditions using an Instron Tensile Analyzer. Under wet conditions, strips are placed in a conical tube containing PBS buffer pH 7.4 at 37°C. The tensile strength of the strips is then measured at 120 minutes, 4 days, 7 days, 11 days, and 14 days.
  • the tensile strength values of the PGLA/PDO materials, as described in Example 1, are shown in Table 2. Table 2.
  • a hemostatic device that combines the PGLA/PDO matrix material and one or more hemostatic agents can be prepared by coating fibrinogen and thrombin onto the PGLA/PDO matrix material of Example 1 for the management of severe bleeding.
  • Such a "Combination Product” is constructed by coating porcine fibrinogen and thrombin onto the PGLA/PDO matrix as described in Example 1.
  • the PGLA/PDO matrix is cut into the size of 5 x 10 cm and sterilized by gamma-irradiation (25 to 35 kGy). Varying amount of porcine fibrinogen and thrombin (see table 3) are mixed thoroughly with about 6.5 ml of HFE-7000.
  • the slurry is poured into a 5.5 x 10.5 cm tray and the PGLA/PDO matrix is immersed in the tray.
  • the coated hemostatic devices are air dried for about 30 minutes.
  • the environmental conditions are maintained at 24C and 45% RH throughout the process.
  • the dressing is vacuum-dried and packed in plastic bag with nitrogen gas.
  • the packed dressing is sterilized again by electronic beam (8 to 12.5 kGy).
  • the efficacy of the dressing is tested in severe bleeding model (swine partial nephrectomy model). The results are presented in Table 3. Table 3.
  • Poly (glycolide-co-lactide) (PGLA, 90/10 mol/mol) is melt-spun into polymeric fiber.
  • a multi-filament yarn is consolidated, crimped and cut into PGLA staple material having a length of 5.1 cm (2.0 inches).
  • the staple materials of PGLA are carded to create a nonwoven batt and compacted to a thickness of about 2.3 mm and a density of about 59 mg/cc.
  • a mild to moderate bleeding model was created by making an incision of 15 mm long and 3 mm deep on a swine spleen.
  • the PGLA matrix is applied to the surgical site and tamponade is applied for two minutes.
  • Hemostasis is checked for 30 seconds after the two-minute tamponade. If free flow bleeding is not observed within 30 seconds, the time to hemostasis was noted. If free flow bleeding is observed, a 30-second tamponade is reapplied until hemostasis is achieved or until the testing period reaches ten minutes, which is defined as a failure in hemostasis. Two samples were tested and both achieved hemostasis (5.5 and 4.75 minutes).

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Claims (18)

  1. Tissu hémostatique synthétique comprenant au moins un agent hémostatique dans une seule couche non tissée d'un premier tissu absorbable qui comprend un copolymère de polyglycolide/polylactide et d'un deuxième tissu absorbable qui comprend une polydioxanone, dans lequel les deux tissus sont sous forme de fibres discontinues et ledit tissu hémostatique synthétique est exempt de tout matériau polysaccharide cellulosique ou oxydé.
  2. Tissu hémostatique synthétique selon la revendication 1, dans lequel le premier tissu absorbable consiste essentiellement en un copolymère de glycolide/lactide selon une composition de 90/10 mol/mol.
  3. Tissu hémostatique synthétique selon la revendication 2, dans lequel le premier tissu absorbable se compose de fibres discontinues ayant une longueur de 1,9 à 6,4 cm (0,75 à 2,5 pouces).
  4. Tissu hémostatique synthétique selon la revendication 1, dans lequel l'agent hémostatique comprend une thrombine.
  5. Tissu hémostatique synthétique selon la revendication 1, dans lequel la fibre discontinue est ondulée.
  6. Tissu hémostatique synthétique selon la revendication 4, dans lequel le deuxième tissu absorbable se compose de fibres discontinues ayant une longueur de 1,9 à 6,4 cm (0,75 à 2,5 pouces).
  7. Tissu hémostatique synthétique selon la revendication 6, dans lequel la fibre discontinue est ondulée.
  8. Tissu hémostatique synthétique selon la revendication 4, dans lequel l'agent hémostatique comprend en outre un fibrinogène.
  9. Tissu hémostatique synthétique selon la revendication 1, dans lequel le rapport pondéral des fibres discontinues du premier tissu contre les fibres discontinues du deuxième tissu est de 70:30.
  10. Tissu hémostatique synthétique selon la revendication 9, dans lequel le mélange des fibres discontinues est compacté jusqu'à une épaisseur d'environ 1,5 mm.
  11. Tissu hémostatique synthétique selon la revendication 10, dans lequel le mélange des fibres discontinues est compacté jusqu'à une densité d'environ 100 mg/cm3.
  12. Agent hémostatique destiné à une utilisation dans un procédé visant à produire une hémostase par application dudit agent hémostatique dans un tissu hémostatique synthétique sur un tissu ou une plaie nécessitant une hémostase, ledit tissu hémostatique synthétique comprenant au moins un dudit agent hémostatique dans une seule couche non tissée d'un premier tissu absorbable comprenant un copolymère de polyglycolide/polylactide et d'un deuxième tissu absorbable comprenant une polydioxanone selon l'une quelconque des revendications précédentes.
  13. Agent hémostatique destiné à une utilisation selon la revendication 12, ladite utilisation comprenant le fait d'assurer la maîtrise et la réduction de saignements légers à modérés dans un délai effectif de 1 à 10 minutes.
  14. Tissu hémostatique synthétique selon la revendication 1 ayant une résistance à la traction (Newton/cm) de :
    a. environ 63 à l'état sec ;
    b. environ 59 à l'état humide pendant 120 minutes ;
    c. environ 50 à l'état humide pendant 4 jours ;
    d. environ 35 à l'état humide pendant 7 jours ;
    e. environ 18 à l'état humide pendant 11 jours ;
    f. environ 11 à l'état humide pendant 14 jours.
  15. Procédé de fabrication d'un tissu hémostatique synthétique selon la revendication 1, comprenant les étapes qui consistent à :
    a. mettre en suspension une thrombine et un fibrinogène dans un hydrocarbure perfluoré pour former une suspension ; et
    b. appliquer la suspension sur le tissu non tissé absorbable.
  16. Procédé selon la revendication 15, dans lequel l'activité de thrombine sur le tissu hémostatique synthétique est d'environ 20 à 500 UI/cm2, et la quantité de fibrinogène sur le pansement est d'environ 2 à 15 mg/cm2.
  17. Procédé selon la revendication 16, comprenant en outre l'étape de stérilisation du tissu hémostatique synthétique.
  18. Procédé selon la revendication 17, dans lequel le pansement de plaie est stérilisé par irradiation.
EP11784012.4A 2010-05-17 2011-05-16 Matrice synthétique absorbable renforcée pour applications hémostatiques Active EP2571540B1 (fr)

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US12/781,103 US8273369B2 (en) 2010-05-17 2010-05-17 Reinforced absorbable synthetic matrix for hemostatic applications
PCT/US2011/036590 WO2011146359A1 (fr) 2010-05-17 2011-05-16 Matrice synthétique absorbable renforcée pour applications hémostatiques

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US20120315316A1 (en) 2012-12-13
US8273369B2 (en) 2012-09-25
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US8383147B2 (en) 2013-02-26
EP2571540A1 (fr) 2013-03-27
MX2012013395A (es) 2012-12-10
WO2011146359A1 (fr) 2011-11-24
CA2799916A1 (fr) 2011-11-24
CN106215217A (zh) 2016-12-14
AU2011256403A1 (en) 2012-12-06
JP2013526368A (ja) 2013-06-24
BR112012029293B1 (pt) 2019-04-24
BR112012029293A2 (pt) 2015-09-22
RU2012154328A (ru) 2014-06-27
ES2659173T3 (es) 2018-03-14
RU2574016C2 (ru) 2016-01-27
CN102892439A (zh) 2013-01-23
AU2011256403B2 (en) 2013-10-03
CA2799916C (fr) 2018-03-13
US20110280919A1 (en) 2011-11-17
JP5905451B2 (ja) 2016-04-20

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